Physical interaction with Spo11 mediates the localisation of
Mre11 to chromatin in meiosis and promotes its nuclease
activity

J 2024

Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity

AITHAL, Rakesh, Kuldeep NANGALIA, Mário ŠPÍREK, Doris CHEN, Franz KLEIN et. al.

Basic information

Original name

Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity

Authors

AITHAL, Rakesh (356 India, belonging to the institution), Kuldeep NANGALIA, Mário ŠPÍREK (703 Slovakia, belonging to the institution), Doris CHEN, Franz KLEIN and Lumír KREJČÍ (203 Czech Republic, belonging to the institution)

Edition

Nucleic acids research, Oxford, Oxford University Press, 2024, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.900 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1093/nar/gkae111

UT WoS

001173092200001

Keywords in English

Spo11; Mre11; Meiosis; Chromatin localization; Nuclease activity

Abstract

V originále

Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties and of its interactions with other DSB proteins. In this study, we have purified fragments of Spo11 and show for the first time that Spo11 can physically interact with Mre11 and modulates its DNA binding, bridging, and nuclease activities. The interaction of Mre11 with Spo11 requires its far C-terminal region, which is in line with the severe meiotic phenotypes of various mre11 mutations located at the C-terminus. Moreover, calibrated ChIP for Mre11 shows that Spo11 promotes Mre11 recruitment to chromatin, independent of DSB formation. A mutant deficient in Spo11 interaction severely reduces the association of Mre11 with meiotic chromatin. Consistent with the reduction of Mre11 foci in this mutant, it strongly impedes DSB formation, leading to spore death. Our data provide evidence that physical interaction between Spo11 and Mre11, together with end-bridging, promote normal recruitment of Mre11 to hotspots and DSB formation.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GX21-22593X, research and development project

Name: Identifikace a charakterizace proteinů zahrnutých v metabolismu G-kvadruplexů a R-smyček a jejich vztah k replikaci DNA

206292/E/17/Z, interní kód MU

Name: Mechanics and execution of homologous recombination - biophysics to the organism

Investor: Wellcome Trust

Citovat

AITHAL, Rakesh, Kuldeep NANGALIA, Mário ŠPÍREK, Doris CHEN, Franz KLEIN and Lumír KREJČÍ. Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity. Nucleic acids research. Oxford: Oxford University Press, 2024, vol. 52, No 8, p. 4328-4343. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkae111.

@article{2387600,
   author = {Aithal, Rakesh and Nangalia, Kuldeep and Špírek, Mário and Chen, Doris and Klein, Franz and Krejčí, Lumír},
   article_location = {Oxford},
   article_number = {8},
   doi = {http://dx.doi.org/10.1093/nar/gkae111},
   keywords = {Spo11; Mre11; Meiosis; Chromatin localization; Nuclease activity},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic acids research},
   title = {Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity},
   url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae111/7614131?login=true},
   volume = {52},
   year = {2024}
}

TY  - JOUR
ID  - 2387600
AU  - Aithal, Rakesh - Nangalia, Kuldeep - Špírek, Mário - Chen, Doris - Klein, Franz - Krejčí, Lumír
PY  - 2024
TI  - Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity
JF  - Nucleic acids research
VL  - 52
IS  - 8
SP  - 4328-4343
EP  - 4328-4343
PB  - Oxford University Press
SN  - 03051048
KW  - Spo11
KW  - Mre11
KW  - Meiosis
KW  - Chromatin localization
KW  - Nuclease activity
UR  - https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae111/7614131?login=true
N2  - Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties and of its interactions with other DSB proteins. In this study, we have purified fragments of Spo11 and show for the first time that Spo11 can physically interact with Mre11 and modulates its DNA binding, bridging, and nuclease activities. The interaction of Mre11 with Spo11 requires its far C-terminal region, which is in line with the severe meiotic phenotypes of various mre11 mutations located at the C-terminus. Moreover, calibrated ChIP for Mre11 shows that Spo11 promotes Mre11 recruitment to chromatin, independent of DSB formation. A mutant deficient in Spo11 interaction severely reduces the association of Mre11 with meiotic chromatin. Consistent with the reduction of Mre11 foci in this mutant, it strongly impedes DSB formation, leading to spore death. Our data provide evidence that physical interaction between Spo11 and Mre11, together with end-bridging, promote normal recruitment of Mre11 to hotspots and DSB formation.
ER  -

AITHAL, Rakesh, Kuldeep NANGALIA, Mário ŠPÍREK, Doris CHEN, Franz KLEIN and Lumír KREJČÍ. Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity. \textit{Nucleic acids research}. Oxford: Oxford University Press, 2024, vol.~52, No~8, p.~4328-4343. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkae111.

Detailed Information on Publication Record